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Series GSE252654 Query DataSets for GSE252654
Status Public on May 17, 2024
Title Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The ubiquitination and proteasome-mediated degradation of Hypoxia Inducible Factors (HIFs) is central to metazoan oxygen-sensing, but the involvement of deubiquitinating enzymes (DUBs) in HIF signalling is less clear. Here, using a bespoke DUBs sgRNA library we conduct CRISPR/Cas9 mutagenesis screens to determine how DUBs are involved in HIF signalling. Alongside defining DUBs involved in HIF activation or suppression, we identify USP43 as a DUB required for efficient activation of a HIF response. USP43 is hypoxia regulated and selectively associates with the HIF-1 isoform, and while USP43 does not alter HIF-1 stability, it facilitates HIF-1 nuclear accumulation and binding to its target genes. Mechanistically, USP43 associates with 14-3-3 proteins in a hypoxia-dependent manner to increase the nuclear pool of HIF-1, independently of DUB activity. Together, our results unveil the DUB landscape in HIF signalling, and highlight the multifunctionality of DUBs, illustrating that they can provide important signalling roles outside of their catalytic activity.
 
Overall design To investigate the transcriptional responses of DUB genes in response to hypoxia, we generated RNA-Seq data sets of control and HIF1B KO cells from normoxic and hypoxic conditions. We also included USP43 KO samples for these conditions as this is a hypoxia-inducible DUB and a hit in our genetic screens.
 
Contributor(s) Pauzaite T, Wit N, Seear R, Nathan JA
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Submission date Jan 05, 2024
Last update date May 18, 2024
Contact name Niek Wit
E-mail(s) nw416@cam.ac.uk
Organization name University of Cambridge
Department Department of Medicine
Lab Professor James Nathan
Street address Puddicombe Way
City Cambridge
State/province Not US or Canada
ZIP/Postal code CB2 0AW
Country United Kingdom
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (18)
GSM8004861 Control hypoxia biol rep 1
GSM8004862 Control hypoxia biol rep 2
GSM8004863 Control hypoxia biol rep 3
This SubSeries is part of SuperSeries:
GSE252655 Deubiquitinating enzyme mutagenesis screens identify a USP43 driven HIF-1 transcriptional response
Relations
BioProject PRJNA1061575

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Supplementary file Size Download File type/resource
GSE252654_RAW.tar 53.9 Mb (http)(custom) TAR (of SF)
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Raw data are available in SRA

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